Tag Archives: hormone side-effects

Effects of different steps in gender reassignment therapy on psychopathology: a prospective study of persons with a gender identity disorder

This study found that hormone therapy reduced symptoms of psychological distress, although surgery had no further effect.

However, this conclusion is undercut by the fact that one person committed suicide during follow-up,* treatment did not reduce the prevalence of suicide attempts, and 17% of the people surveyed after treatment reported suicidal thoughts.

There are also areas where the methodology of the study could be improved.

Finally, the data on the percentages of suicide attempts is confusing. See the end of this review for details on the data.

Summary of the results:

After treatment, patients reported fewer symptoms of anxiety, depression, interpersonal sensitivity, and hostility.

Transition did not reduce the percentage of suicide attempts.

One patient committed suicide during follow-up.*

Transition did not affect patients’ psychosocial well-being, i.e. employment, relationships, number of sexual contacts, drug use, and suicide attempts.

Over 90% of patients said that they were happier and felt better about their body after treatment, but 17% reported that they had suicidal thoughts.

The improvement in psychological symptoms happens after hormone therapy. Surgery did not cause a significant change in psychopathology, although patients reported slightly more symptoms after surgery than after hormone therapy.

When asked, 57.9% of patients said that they experienced the most improvement after hormone therapy, 31.6% experienced the most improvement after surgery, and 10.5% experienced improvement just from being diagnosed.

After treatment, the average scores of psychopathology were similar to the general population.

After hormone therapy, none of the average subscale scores were different from the general population. However, after surgery, the group’s average scores for sleeping problems (p=0.033) and psychoticism (p=0.051) were higher than the general population.

These results raise some important questions.

What can we do to reduce suicide, suicide attempts, and suicidal thoughts in transgender people who have transitioned?

Why didn’t the percentage of suicide attempts go down when people were reporting fewer symptoms of depression?

Why didn’t surgery improve the mental well-being of the patients?

There were also a couple of important methodological questions that the authors did not discuss.

Combining the results of different treatments

As often happens, the study lumped together trans men (born female) and trans women (born male). The treatments for trans women and trans men involve different medications and surgeries. It is possible that androgens and estrogens have different effects on mood. Similarly, it might be that some surgeries are more beneficial to mental health than others or that some surgeries are more stressful than others.

The participants in the study were 46 trans women and 11 trans men. The authors do not discuss whether they differed in their mental health symptoms or social well-being. Nor do they give information on the gender of the people who completed the questionnaires at follow-up.

The study does not specify exactly what medications and dosages were used for the hormone therapy. They do not say exactly what surgeries the patients got.

Missing Data

As with many longitudinal studies, they did not have follow-up data on all of the participants due to incomplete questionnaires. In addition, one participant did not complete a questionnaire at the beginning of the study.

Thus, 56 people completed a questionnaire about their mental health before treatment, but only 47 people completed the questionnaire after hormone treatment. The authors then compared the average scores on the baseline questionnaires to the averages on the questionnaires after hormones.

It is possible that this would lead to a bias in the data. For example if depressed people were less likely to complete follow-up questionnaires, the average for the follow-up questionnaires would show fewer symptoms of depression than the average for the initial questionnaires.

The authors do not discuss whether the people who did not complete the questionnaires after hormone therapy were significantly different from those who did.

Leaving suicide out of the results

The person who committed suicide was not included in the study; if they had been it might have distorted the data. Presumably their responses at baseline would have increased the average score for symptoms of depression, but without a follow-up questionnaire for them, symptoms of depression would appear to go down. Leaving them out makes the results clear – symptoms of depression went down among everyone else.

At the same time, without data on the person who committed suicide during follow-up, it is not fully accurate to say that symptoms of depression went down after treatment. For at least one person it doesn’t make sense to talk about symptoms of depression going down.

Suicide during follow-up is part of the results of this study. It is relevant to the question of whether or not people felt better after transition. When someone commits suicide during a study, this needs to be part of the discussion. When did they commit suicide? Were they depressed before transition? Did they regret the surgery? Did they say they were depressed during or after transition?

Not talking about the suicide is disrespectful to the person who died. It leads to possibly false conclusions about the effects of transition. And it stops us from being able to figure out what we can do to prevent future suicides – do we need to give people more therapy before medical treatments? should some people not get surgery? do we need to give people more therapy after surgery?

Back to the questions raised by the study

What can we do to reduce suicide, suicide attempts, and suicidal thoughts in transgender people who have transitioned?

Clearly, medical transition is not enough. It does not prevent suicide, suicide attempts, or suicidal thoughts. It does not even reduce the prevalence of suicide attempts.

As far as I know, this is the only study that has followed a group of people with gender dysphoria during treatment and collected data on suicide attempts.

We need more research to figure out how to prevent suicide and suicide attempts among transgender people after transition. It might also help if we knew more about what was going on in this study.

When exactly were the suicide attempts – after hormones or after surgery? When exactly did the person commit suicide?  Does this reflect regret related to the surgery itself or something else?

Were there any gender differences in the suicide attempts?

Were there any differences in the specific treatments given to the people who attempted suicide? Were there any problems in the outcomes of the treatments?

Did the same people attempt suicide before and after transition?

Did the people who attempted suicide say they were depressed? Had they been diagnosed with mental health issues? Were they getting counseling?

Do we know of things that went wrong in the lives of the people who attempted suicide?

Do some people need more counseling and evaluation before transition? Should we adapt the hormonal doses or surgeries for different people? Do we need to give additional support after transition? Are there alternatives to transition that would better help some people deal with gender dysphoria?

At this point all we know is that we can not rely on medical transition to prevent or reduce suicide attempts among transgender people.

We need to know more.

Why didn’t the percentage of suicide attempts go down when people were reporting fewer symptoms of depression?

The results of this study are somewhat confusing. People reported that their symptoms of depression and psychological distress went down after transition. In addition, the vast majority of people who had transitioned said that they felt better – they were happier (93%), less anxious (81%), more self-confident (79%), and their body-related experience improved (98%). Only 2 people said they were more anxious and 1 less self-confident. Only 2 said that their overall mood was similar.

So why did 7 people (17.6%) report that they had suicidal thoughts? Why were there 4 suicide attempts?

Were the people who had suicidal thoughts so unhappy to start with that an improvement in their mood still left them suicidal? Perhaps they had even more suicidal thoughts before transition – but the prevalence of suicide attempts was not affected by transition.

It’s possible that the group’s average scores for depression are in the normal range while a few individuals are miserable. On the other hand, the group has an above average number of suicide attempts and suicidal thoughts. According to an Emory University website “It is estimated that 3.7% of the U.S. population (8.3 million people) had thoughts of suicide in the past year, with 1.0% of the population (2.3 million people) developing a suicide plan and 0.5% (1 million people) attempting suicide.” In this study, 17.6% of the group reported suicidal thoughts at the moment of follow-up. The suicide attempt percentage was 9.8% at follow-up.

We are looking at a group of people with elevated levels of suicidal thoughts and suicide attempts – how does that fit with questionnaires that find a normal level of symptoms of depression?

Are we seeing accurate reports of how people feel? Are people minimizing their problems when they fill out questionnaires after treatment?

The authors of the study do not discuss the apparent contradiction between suicide attempts and suicidal thoughts one the one hand and an improved mood on the other.

The authors do point out that the percentage of suicide attempts at the beginning of the study was lower than in other studies of transgender people. It may be that the participants in this study had fewer problems than most transgender people; for one thing they are a group that is able to access medical care. However, that does not answer the question of why for this particular group of people transition did not change the prevalence of suicide attempts.

We need more research into what is going on here. We need to be able to identify people who may attempt suicide or feel suicidal after transition so we can help them.

Why didn’t surgery improve the mental well-being of the patients?

We don’t know and we need more research to answer this question. However, here are a few possibilities:

Possibility #1 – Return to regular life

In their discussion, the authors suggest that there might be an initial euphoria after beginning hormones that wears off later on. In addition, after surgery, people might be “again confronted with stigma and other burdens.”

In other words, the improvement after hormone therapy is higher than the improvement will be in the end. There is still an improvement later on, but the initial level of euphoria isn’t going to last. If this is true, it would be important information for people who are transitioning so that they don’t have false expectations of what life will be like after transition is complete.

Possibility #2 – Surgery is not the best treatment for everyone

The authors also suggest that further studies should look at exploring the idea that some patients might want hormones without surgery.

It may be that surgery is not the best treatment for everyone with gender dysphoria. Perhaps some people would have been better off with just hormone therapy.

Previous studies have found that about 3% of people who have had genital surgery regret it, so we would expect one or two people out of 50 to regret their surgery. Perhaps they are depressed and this affects the group average.

Possiblity #3 – Effects of surgery

It is also possible that some people had post-surgical depression and that this affected the results.

Perhaps some people were still recovering from surgery and did not feel well (the study included people 1 to 12 months after surgery). In particular, this might lead to the increase in sleeping problems found in the study.

Perhaps some people were dealing with complications of surgery.

Perhaps the hormonal changes after surgery affected people’s moods.

Possibility #4 – People were already happy

On the other hand, perhaps by the time people get surgery, they are already happy due to counseling, hormones, and social transition.

Perhaps if people had been forced to stop with hormone therapy alone, they would have become unhappy.  As the authors point out, it may have made a difference that they knew they were going to be able to get surgery.

Possibility #5 – Surgery doesn’t affect mental health

It may simply be that surgery does not improve mental health. At this point, we do not have proof that it does.

In the end, we just don’t know.

Further studies are needed to determine if surgery is helpful and who should get it. Perhaps the authors of this study can use the data they already have to address this question.


* Data on this patient was not included in the study.

Original Source:

Effects of different steps in gender reassignment therapy on psychopathology: a prospective study of persons with a gender identity disorder by Gunter Heylens, Charlotte Verroken, Sanne De Cock, Guy T’Sjoen, Griet De Cuypere in J Sex Med 2014 Jan 28;11(1):119-26. Epub 2013 Dec 28.


Questions about the data on suicide attempts:

The authors talk about the prevalence of suicide attempts before and after transition, but they don’t talk about the time periods they are looking at. The authors say that the prevalence of suicide attempts was unchanged, but they don’t explain when the suicide attempts took place before treatment. It makes a big difference if they are comparing three years before transition to three years afterward or if they are comparing a lifetime before transition to the average 3 year follow-up period – a follow-up that took place 1-12 months after surgery.

In addition, the actual data on suicide attempts is confusing. In Table 3, the authors list the prevalence of suicide attempts as 9.4% at presentation and 9.3% at follow-up. However, in their discussion they say the suicide attempt percentages were 10.9% initially and 9.8% at follow-up.

Looking at Table 3,  there were 5 attempts in a group of 54 people which would give a percentage of 9.26%, a number that doesn’t match either of the ones given by the authors. In addition, there were 4 attempts in a group of 42 people which would give 9.52%, another number that doesn’t match.

The percentage they gave at baseline in Table 3 seems to be 5 out of 53 people, while the percentage at follow-up seems to be 4 out of 43. Perhaps one of the 54 people didn’t answer the question on suicide attempts in the first set of questionnaires. But where does the additional person come from in the second set of questionnaires? If they are including the person who committed suicide in the suicide attempts, wouldn’t the number of people used to calculate the percentage before treatment be 54 or 55, not 53?

None of this explains why they would list different numbers in their discussion. Perhaps there were some suicide attempts by the same person that were included in one set of numbers but not the others? The table talks about the prevalence of suicide attempts while the discussion talks about the percentage.

It would have been helpful if they had clarified this.



A brain sexual dimorphism controlled by adult circulating androgens

This is a study about rats. As always, we don’t know if what works for them is true of humans. The study does, however, point to an important factor to consider in any research on gender identity.

The authors found that they could completely change an observed sex difference in adult rats’ brains by changing their sex hormones. Earlier exposure to sex hormones made no difference.

This means that this observed sex difference was completely caused by adult circulating androgens.

The authors suggest that this might also happen in human brains. They refer to studies of the structures in transsexual brains and suggest that we can’t be sure that observed differences were caused by differences in the early development of the brain. They might have been caused by taking cross-sex hormones.

This study is from 1999, so they are referring to some of the early work on gender identity and the brain by Swaab et al and Zhou et al. Those studies included the brains of trans people who had been taking hormones.

Those studies are probably obsolete; newer studies have indeed found that taking sex hormones changes human brains, including the area Swaab et al and Zhou et al talked about, the hypothalmus.

This study of hormones in adult rat brains would not affect studies if they a) look at trans people who have not yet taken any hormones and b) test people to make sure their hormonal levels are in the normal range for their biological sex.*

It is also possible that some areas of the brain are controlled by circulating hormones and some are affected by earlier exposure to hormones as well as circulating hormones. The authors cite examples where castration dramatically changed areas of the rat brain, but did not completely reverse the sex difference.

The authors also discuss studies that found you could change a bird’s brain by changing its hormones.

They conclude by discussing the ways adult hormones affect the human brain.

“Human behavior is also subject to the activational effects of androgens. Transsexuals treated with cross-sex hormones display sex reversals in their cognitive abilities, emotional tendencies, and libido (34, 35), and sex offenders are sometimes treated with antiandrogens to reduce their sex drive (36). The sociosexual changes observed in these groups most likely reflect structural and physiological plasticity in steroid-sensitive areas within the brain. The volumetric sex reversal reported here substantiates the possibility that hormones in adulthood can dramatically affect the structure of a brain region concerned with sexual behavior. Although the volumetric sexual dimorphism of the MePD is more modest than other animal models [a difference of 150% rather than 400–600% (31)], the extent of the MePD sexual dimorphism in rats in quite comparable to reported sexual dimorphisms in the human brain (1–6) and therefore supports the possibility that sexual dimorphisms of the human brain are caused solely by circulating steroids in adulthood.”

We can’t generalize from a study of rat brains to human brains, but this study does underline the importance of using trans people who have not taken cross-sex hormones if you want to study gender identity and the brain.

Original Article:

A brain sexual dimorphism controlled by adult circulating androgens by Bradley M. Cooke, Golnaz Tabibnia, and S. Marc Breedlove in Proc. Natl. Acad. Sci. USA Vol. 96, pp. 7538–7540, June 1999.

*A Japanese study found that many of the female-to-male transsexuals applying to their clinic had polycystic ovarian syndrome (PCOS); PCOS causes high levels of androgens.

(Bold added by George Davis.)

Effects of cross-sex hormone treatment on cortical thickness in transsexual individuals – Review of Abstract

This is an interesting study that found that taking cross-sex hormones changed the thickness of the cortex in the brain.

I have only been able to see the abstract; the study was published in May 2014 and I do not have access to it.

The study looked at 15 trans men (born female) before and after they took testosterone for at least six months. They also looked at 14 trans women (born male) before and after they took androgen blockers and estrogens for at least six months.

They found that :

“After testosterone treatment, FtMs (trans men) showed increases of CTh bilaterally in the postcentral gyrus and unilaterally in the inferior parietal, lingual, pericalcarine, and supramarginal areas of the left hemisphere and the rostral middle frontal and the cuneus region of the right hemisphere. There was a significant positive correlation between the serum testosterone and free testosterone index changes and CTh changes in parieto-temporo-occipital regions. In contrast, MtFs (trans women), after estrogens and antiandrogens treatment, showed a general decrease in CTh and subcortical volumetric measures and an increase in the volume of the ventricles.”

In other words, taking testosterone makes certain areas of your brain thicker and more testosterone changes your brain more.

Blocking testosterone and taking estrogens makes certain areas of your brain shrink. According to the abstract, this makes the ventricles get bigger – the ventricles are a network of cavities in the brain that contain cerebrospinal fluid.

We already know that there are sex differences in the thickness of the brain’s cortex, although we don’t know exactly what they mean. (You can read more about cortical thickness and what it might mean here.)

Thus study suggests that some of the sex differences we observe in the brain are related to the hormones in our bodies. Our brains are not set in stone by pre-natal exposure to hormones.

For transgender people this study shows that hormone therapy will change your brain.

It does not tell us what that will means in terms of changes in thoughts, feelings, or behaviors.

It’s also not clear if the changes in the trans women’s brains are caused by reducing the testosterone level or adding estrogen or both.

The abstract does not discuss whether the changes caused by the cross-sex hormones make the brain more “masculine” or “feminine” or neither.

It looks like this study is a follow-up to an earlier study, Cortical Thickness in Untreated Transsexuals. The earlier study found that before hormone therapy there were differences between transsexuals and control groups.

The differences the authors found in their earlier study were fairly complicated:

“We would suggest that transsexuals do not show a simple masculinization (FtMs) or feminization (MtFs) of their brains—rather, they present a complex picture in their process of sexual differentiation depending on the brain region studied and the kind of measurements taken.”

In other words, there were some ways in which trans men have brains like cis men’s and some ways in which their brains are like cis women’s while trans women have brains that are like cis women’s in some ways and like cis men’s in others.

One caveat to the pre-hormone part of the study – the authors only included people who were “erotically attracted to subjects with the same anatomical sex.” Thus, it is possible that the brain differences they observed were caused by sexual orientation, not gender identity.

Many studies of gender identity and the brain make this mistake. For example, they will compare a group of trans men who are attracted to women to a group of cis men who are attracted to women and a group of cis women who are attracted to men. It makes it impossible to be sure if any differences between the brains of trans men and cis women are due to gender identity or sexual orientation.

Studies of gender identity and the brain should include control groups of lesbians and gay men as well as straight people.

In any case, the current study shows that taking cross-sex hormones will further change the brain.

Original Article (Abstract):

Effects of cross-sex hormone treatment on cortical thickness in transsexual individuals by Zubiaurre-Elorza L, Junque C, Gómez-Gil E, Guillamon A in J Sex Med. 2014 May;11(5):1248-61.

Related blog post – Increased Cortical Thickness in Male-to-Female Transsexualism – A Review and a Hypothesis.

Bilateral Non-arteritic Ischemic Optic Neuropathy in a Transsexual Woman Using Excessive Estrogen Dosage – Review

This is a study of a trans woman who went blind, probably because she gave herself an overdose of estrogen which caused her to have a stroke. In addition to losing her sight, she is no longer able to take any estrogen.

The main conclusion from this study is follow your doctor’s advice when it comes to taking hormones.

The article goes into a detailed discussion of the individual case and their diagnosis and treatment of the trans woman. The patient was in her early 50s and had been diagnosed with gender dysphoria. Her doctor had already started her on androgen blockers.

The trans woman had a history of type 2 diabetes, hypertension, obesity, and smoking. She was taking metformine 850 mg BID, glimepride 3 mg OD, and insulin therapy (NPH 12 Units OD.

These factors suggested that hormone therapy would be risky for her. The doctors put her on a low dose of transdermal estrogens and encouraged her to adopt a more healthy lifestyle.

The patient was doing well at losing weight and quitting smoking. Her hypertension persisted and she was given lisinopril 20 mg OD for it.

However, she was not doing well emotionally and was admitted to the Department of Psychiatry for several months for depression and “personality problems.” (I’m not sure what that last bit means.) The patient had been diagnosed previously with “mixed personality disorder with mainly cluster B traits” in addition to her gender dysphoria.

After 10 months of hormone therapy, the patient lost sight in one eye; six months later she lost some of her vision in the other eye. At this time they discovered that her estrogen levels were very high. The patient admitted that she had overdosed herself because she was impatient for feminization.

The authors conclude:

Both oral contraceptives in premenopausal and hormone replacement therapy in postmenopausal women are known to increase the risk for cardiovascular diseases, including cerebrovascular diseases (Sare, Gray, & Bath, 2008). Other cardiovascular risk factors, such as smoking, hypercholesterolemia, hypertension, and type 2 diabetes, play an even more important role (Lindenstrøm, Boysen, & Nyboe, 1993). It is advised that cardiovascular risk factors should be monitored and treated in transsexual persons before initiation of cross-sex hormone treatment (Hembree et al.,2009); however, no recommendations are available on a dosage reduction in sex hormone treatment in patients with cardiovascular risk factors.

In conclusion, we presented a case of bilateral non-arteretic anterior ischemic optic neuropathy possible associated to excessive estrogen therapy in a transsexual woman with co-morbidities. It is highly likely that these high estradiol levels were related to the cerebrovascular thrombosis and also played a role in development of the bilateral sequential NA-ION.

The authors suggest that cardiovascular risk factors should be monitored and treated before starting cross-sex hormone therapy. This is, of course, good advice.

However, the problem here was that the patient went against her doctor’s orders and overdosed on hormones. I would add a few conclusions to theirs:

1. Patients should follow their doctors orders when it comes to hormone doses.

2. Doctors should be aware that some patients may be extremely distressed and behave irrationally. They should clearly explain how long feminization takes and just as importantly, provide supportive therapy throughout the process.

3. Doctors and patients must work together as a team. Both doctors and patients have a role to play in creating that team. Patients must cooperate and be honest; doctors must earn the trust of patients.

4. We need more research on the safety of hormones and dosages for people who are older and/or in bad health.

5. We need more research on how to help someone with gender dysphoria who is unable to take hormones or who must take them at a low dosage.

Bold added by George Davis.

Orignal Article:

Bilateral Non-arteritic Ischemic Optic Neuropathy in a Transsexual Woman Using Excessive Estrogen Dosage by Wierckx K, De Zaeytijd J, Elaut E, Heylens G, T’Sjoen G. in Arch Sex Behav. 2014 Feb;43(2):407-9. doi: 10.1007/s10508-013-0187-9. Epub 2013 Sep 21.